RNA aptamers selected against amyloid β-peptide (Aβ) inhibit the aggregation of Aβ

Abstract

Aggregation of amyloid β-peptide (Aβ) is closely related to the pathogenesis of Alzheimer’s disease (AD). Much effort has been devoted to the construction of molecules that suppress and neutralize the toxicity of Aβ. Using a systematic evolution of ligands using the exponential enrichment (SELEX) procedure, we have constructed RNA aptamers that bind to Aβ1-40 and inhibit aggregation. To obtain the RNA aptamers, we applied an oligomer model of Aβ as a selection target using Aβ1-40 conjugated with a colloidalgold nanoparticle (Aβ–AuNP). Although the selected RNA sequences did not converge, two RNA aptamers (N2 and E2) bound more tightly to Aβ–AuNP than the other aptamers. The dissociation constants (K_d) of N2-Flu and E2-Flu, fluorescent-labeled RNAs, to monomeric Aβ1-40 peptide were estimated as K_d = 21.6 and 10.9 μM, respectively. ELISA revealed that these aptamers can inhibit Aβ aggregation efficiently. Transmission electron micrographs indicated that N2 and E2aptamers can stop the fibrillization of Aβ1-40. The selected RNA aptamers may have potential as therapeutic agents for AD pathogenesis.